EXCHANGE 


New  Hydroxamic  Acids  Derived  from 

Cyclopropane  Carboxylic  Acid,  Iso- 

butyric  Acid  and  Dibenzyl-Acetic 

Acid.     A  Comparative  Study  of 

the  Beckmann  Rearrangement 

of  Their  Derivatives 


KVCHANGE 

nrT  3    1922 


ALFRED  WITHERSPOON  SCOTT 


OP  THE 

V     DIVERSITY 
% 


New  Hydroxamic  Acids  Derived' from 

Cyclopropane  Carboxylic  Acid,  Iso- 

butyric  Acid  and  Dibenzyl- Acetic 

Acid.     A  Comparative  Study  of 

the  Beckmann  Rearrangement 

of  Their  Derivatives 


A  DISSERTATION 
PRESENTED  TO  THE 

FACULTY  OF  PRINCETON  UNIVERSITY 

IN  CANDIDACY  FOR  THE  DEGREE 

OF  DOCTOR  OF  PHILOSOPHY 

BY 

ALFRED  WITHERSPOON  SCOTT 


NEW  HYDROXAMIC  ACIDS  DERIVED  FROM  CYCLOPROPANE 
CARBOXYLIC  ACID,  ISOBUTYRIC  ACID  AND  DIBENZYL-ACETIC 
ACID.     A    COMPARATIVE    STUDY    OF    THE    BECKMANN    RE- 
ARRANGEMENT OF  THEIR  DERIVATIVES.1 

I.     Introduction. 

Although  many  different  classes  of  organic  compounds  show  rearrange- 
ments of  the  Beckmann1  type,  there  is  one  fundamental  transformation 
which  stands  out  as  essential  to  all  such  reactions ;  some  radical,  R,  attached 
to  a  carbon  atom  in  the  original  compound,  is  found  in  combination  with 
a  nitrogen  atom  after  the  rearrangement  has  occurred.  If  oximes  are 
excluded,  a  general  formula  may  be  employed  to  represent  the  classes 
of  compounds  which  show  such  changes. 

R     x  R 

ii         v  r  x 

C— N— y     >•          yC— N—      +     xy     >  >C=N— R      +     xy 

b/  b/ 

I  II  III 

The  symbols  a  and  b  stand  for  R2,  O=,  HN=,  and  for  similar  groups; 
while  x  and  y  may  be  replaced  by  H  or  a  metal  atom  together  with  some 
other  radical  such  as  Cl,  Br,  OH,  OCOR.  In  the  azides,  N2=  takes  the 
place  of  x  and  y. 

For  several  years,  plain  structural  formulas  of  'this  kind  have  been 
replaced  by  electronic  formulas2  in  which  positive  and  negative  signs  serve 
to  represent  bonds  between  atoms.  In  an  article3  recently  published  in 
the  J.  Am.  Chem.  Soc.,  the  rearrangement  of  a  hydroxamic  acid  deriva- 
tive was  represented  by  symbols  more  in  harmony  with  recent  views 
concerning  the  structure  of  the  atom  and  the  nature  of  "bonds"  in  organic 
compounds.  Thus: 

R    x  R 

;o;    C:N:y    — >    :Q:C:N:     +     x:y     — >     :Q:C:N''        +    x:y 

'.'.••  I       I       I       '.  K. 

la  Ila  Ilia 


1  In  this  article,  the  term  Beckmann  rearrangement  is  used  in  its  broadest  sense 
and  includes  rearrangements  of  the  Hofmann,  of  the  Curtius  and  of  the  Lessen  types. 

2  Jones,  Am.  Chem.  J.,  48,  25  (1921);     50,  441  (1913);     /.  Am.  Chem.  Soc.,  36, 
1268  (1914).     Stieglitz,  ibid.,  36,  288  (1914). 

3  Jones  and  Hurd,  /.  Am.  Chem.  Soc.,  43,  2424  (1921). 


408    '     [\     [   *     ;*  ^   "  ..;: 

It  has*  been  assumecf  for  some  time  that,  during  the  reaction,  the  radical  R 
separates  from  the  carbon  atom  and  "wanders"  to  the  univalent  nitrogen 
atom  (Ha)  not  because  of  "any  complicated  mechanism"  such  as  ring 
formation,  a  bivalent  carbon  radical,  or  the  like,4  but,  rather,  under  the 
influence  of  electrical  constraint  brought  about  by  the  necessity  for  re- 
distribution of  electrons3  to  form  the  more  stable  system  represented  by 
the  isocyanate  stage  (Ilia)  in  the  reaction. 

If  this  be  the  case,  then,  while  the  positive  radical  R  is  shifting  its  posi- 
tion from  the  carbon  atom  to  the  nitrogen  atom,  it  must  exist  momentarily 
as  a  free  radical.  An  hypothesis  which  follows  logically  as  a  consequence 
of  this  conclusion  was  advanced  in  the  article  mentioned  above;4  viz., 
that  an  intimate  relation  must  exist  between  the  ease  of  rearrangement 
of  the  univalent  nitrogen  derivative  (Ha)  and  the  ability  of  the  radical 
R  to  exist  as  Sifree  radical  (e.  g.,  triphenylmethyl,  tri-biphenylmethyl,  etc.). 
Furthermore,  this  assumption  suggests  definite  experiments  which  are 
now  being  tried  in  this  laboratory.  If  certain  azides,  RCONa,  are  caused 
to  undergo  rearrangement  in  a  solution  which  contains  a  group  such  as 
triphenylmethyl,  it  seems  probable  that  this  free  radical  may  compete 
with  the  radical  R  for  possession  of  the  nitrogen  position  and,  conse- 
quently, that  two  isocyanates  may  be  formed  instead  of  one. 
R  R 

|  |  ^r  0=C=N— R  +  Ri  +  N2 

0=C— Ni  +  R'  — >  O=C— N=  +  N2  +  R' 

""»-  O=C=N— R1  +  R  +  N2 

Thus,  with  benzoyl  azide,  C6H6CON3,  and  triphenylmethyl,  both  phenyl 
isocyanate  and  triphenylmethyl  isocyanate  would  be  expected.  The 
results  of  these  experiments  will  be  published  later. 

The  compounds  described  in  this  paper  were  prepared  and  studied  for 
the  purpose  of  determining  the  influence  which  certain  hydrocarbon 
radicals  would  exert  in  producing  variations  in  the  ease  of  rearrange- 
ment of  several  related  hydroxamic  acid  derivatives. 

For  this  purpose,  the  following  series  of  hydroxamic  acids  was  prepared. 
With  the  exception  of  (d),  the  parent  substances  were  new  compounds. 
(a)       -H3Cv  (b)         H2Cv 

^CHC(O)NHOH  |    ;>CHC(O)NHOH 

H3C/  HtC' 

/sobutyr-hydroxamic  Cyclopropane-carboxyl-hydrox- 

Acid  amic  Acid 

(c)  C6H6CH2y  (d)         C,H6CH2CH2C(O)NHOH 

\CHC(0)NHOH 
C,H6CH/ 
Dibenzylacet-hydroxamic  Benzylacet-hydroxamic 

Acid  Acid 

4Stieglitz  (Hesse),  Am.  Chem.  J.,  29,  57  (1903).     Nef,  Ann.,  298,  308  (1897); 
318    (1901).     Jones,    Ref.    3. 


4P9 


Compound  (d)  was  studied  by  Thiele  and  Pickard6  and  the  behavior  of  some 
of  its  derivatives  described.  This  acid  was  included  in  the  series  in  order 
to  be  able  by  comparison  to  determine  more  definitely  the  effect  of  the 
second  benzyl  group  in  Compound  (c). 

The  preparation  of  tribenzylacetic  acid  was  undertaken  in  order  to 
note  the  effect  of  three  benzyl  groups.  For  this  purpose,  tribenzylmethyl 
chloride  was  synthesized.  However,  since  this  chloride  failed  to  react 
to  give  a  Grignard  reagent,  we  have  not  synthesized  tribenzylacetic  acid; 
so  the  study  of  tribenzylacet-hydroxamic  acid  and  its  derivatives  was 
discontinued  for  the  present. 

The  reactions  of  the  potassium,  sodium,  and  silver  salts  of  the  acetyl 
esters  and  of  the  benzoyl  esters  of  the  parent  substances  were  used  for 
comparison.  Dry  salts  of  this  kind  usually  have  a  fairly  definite  tem- 
perature at  which  they  puff  or  explode  to  form  an  isocyanate  and  an  acetate 
or  benzoate.  However,  the  length  of  time  the  salts  have  been  kept  after 
their  preparation  frequently  alters  perceptibly  the  temperature  at  which 
this  change  occurs. 

In  order  to  avail  ourselves  of  a  somewhat  more  reliable  source  of  in- 
formation concerning  the  ease  of  rearrangement  of  these  salts,  the  effect 
of  heat  upon  clear  aqueous  solutions  of  the  potassium  and  the  sodium 
salts  was  also  studied.  Under  these  circumstances,  the  isocyanate  first 
produced  is  usually  converted  into  the  corresponding  s;yw.di-substituted 
urea 

2  O=C=N=R  +  H2O  — >  O=C=(NHR)2  +  CO2. 

II.     Comparison  and  Interpretation  of  Results. 

The  following  table  shows  the  temperatures  at  which  sudden  decomposi- 
tion of  the  dry  salts  occurred. 


TABLE  I 
DECOMPOSITION  TEMPERATURES 


Parent 

hydroxamic 

acids 


(CH,),CHCONHOH  (a) 


(C3H6)CONHOH  (b) 
(C6H6CH2)2CHCONHOH  (c) 


Benzoyl  Ester                         Acetyl  Esi 

K 

Salt 

Na 
Salt 

Saft 

K 

Salt 

Na 
Salt 

Sponta- 

75° 

Above 

Sponta- 



neous 

200° 

neous 

Above 

103° 

143° 

200° 

155° 



Not 

Not 

143° 

Not 

Not 

isolated 

isolated 

isolated 

isolated 

145' 


These  substances  may  be  regarded  as  derivatives  of  acet-hydroxamic 
acid.  On  the  other  hand,  Compounds  (b)  and  (c)  bear  a  structural  relation 
to  wobutyr-hydroxamic  acid  (a). 

5  Thiele  and  Pickard,  Ann.,  309,  197  (1921). 


In  the  interpretation  of  this  table,  we  shall  make  the  assumption  that 
extreme  ease  of  rearrangement  explains  the  failure  to  isolate  some  of  the 
salts  of  (c).  No  doubt,  the  failure  to  obtain  these  salts  may  be  attributed, 
in  part,  to  their  solubility  in  alcohol-ether  in  which  they  were  prepared. 
From  a  general  survey  of  the  table,  it  appears  that,  in  every  case,  the 
derivatives  of  (c)  were  found  to  undergo  rearrangement  with  the  greatest 
ease;  that  the  compounds  of  (b)  required  the  highest  temperature  to 
effect  their  rearrangement ;  and  that  the  salts  of  (a)  occupy  an  intermediate 
position.  It  is  interesting  to  note,  that,  in  the  case  of  the  salts  of  each 
hydroxamic  acid  ester  (dihydroxamic  acid)  the  ease  of  rearrangement 
was  as  follows:  K  >  Na  >  Ag. 

Two  salts,  both  derivatives  of  (a) ,  exhibited  properties  worthy  of  special 
mention.  A  pure  sample  of  the  potassium  salt  of  the  benzoyl  ester  of 
wobutyr-hydroxamic  acid  was  made  and  placed  in  a  desiccator.  The 
desiccator  was  evacuated,  and  in  less  than  20  minutes  the  salt  decomposed 
spontaneously  with  such  violence  as  to  scatter  potassium  benzoate  through- 
out the  entire  container. 

The  potassium  salt  of  the  acetyl  ester  of  (a)  exhibited  the  same  phenom- 
enon, although,  in  this  instance,  it  was  necessary  for  the  salt  to  stand  in 
an  evacuated  desiccator  from  5  to  6  hours  before  the  change  occurred. 
Two  similar  cases  have  been  described  previously;  viz.,  the  potassium  salt 
of  the  benzoyl  ester  of  phenylacet-hydroxamic  acid6  and  the  sodium  salt 
of  the  benzoyl  ester  of  dichloro-acet-hydroxamic  acid.7 

In  studying  the  second  method  of  comparison  of  the  different  salts 
given  in  Table  I,  it  was  found  that  the  temperature  required  to 
produce  a  precipitate  in  an  aqueous  solution  of  the  potassium  salt,  also 
caused  a  precipitate  with  an  aqueous  solution  of  the  sodium  salt  of  the 
same  hydroxamic  acid  ester.  Therefore,  the  table  given  in  Table  II  was  con- 
densed in  order  that  the  behavior  of  these  compounds  could  be  seen  at  a 
glance. 

Rearrangement  was  determined  by  measuring  the  temperature  at  which 
clear  aqueous  solutions  (approximately  equivalent)  of  the  salts  of  alkali 
metals  began  to  give  a  precipitate.  The  components  of  the  precipitate 
were  determined.  In  the  case  of  the  cyclopropane  series,  about  75%  of 
the  corresponding  hydroxamic  ester  was  found  to  be  regenerated.  The 
presence  of  this  proportion  of  the  ester  showed  that,  to  a  large  extent, 
simply  hydrolysis  of  the  salt  had  taken  place,  and  that  rearrangement 
to  give  the  isocyanate  and  then  the  urea  was  distinctly  a  secondary  re- 
action. In  the  wobutyric  acid  series,  similar  products  of  hydrolysis  were 
also  detected;  here,  however,  the  urea  was  the  primary  product  and  the 
regenerated  ester  occurred  in  almost  negligible  amounts  A  more  detailed 

6  Jones,  Am.  Chem.  J.,  48,  8  (1912). 

*  Jones  and  Sneed,  /.  Am.  Chem.  Soc.,  39,  670  (1917). 


411 

description  of  the  treatment  to  which  these  salts  were  subjected  will  be 
found  in  the  experimental  part.  The  temperatures  recorded  in  the  table 
are  those  of  the  bath  employed  in  heating  the  vessel  which  contained  the 
different  solutions. 

TABLB  II 

Parent  Hydroxamic  Aqueous  Solutions  of  the  Potassium 

Acids  or  Sodium  Salts  of  the  Benzoyl  Esters 

0  c. 

(CH3)2CHCONHOH  (a)  50  chiefly  rearrangement 

(C3H5)CHCONHOH  .          (b)  90  mainly  hydrolysis 

(C6H5CH2)2CHCONHOH  (c)  20  rearrangement 

(C6H5CH2)CH2CONHOH  (d)  80  rearrangement 

It  may  be  seen  that,  insofar  as  the  ease  of  arrangement  is  concerned, 
the  results  of  this  table  agree  fairly  well  with  those  of  Table  I.  Since  the 
acyl  group  was  always  the  same  (viz.,  benzoyl)  and,  from  Table  II,  we  see 
that  the  metal  atom  caused  no  appreciable  difference  in  reactivity,  we  are 
forced  to  the  conclusion  that  the  variations  in  behavior  of  these  compounds 
must  be  attributed  to  the  influence  of  the  hydrocarbon  radicals  of  the 
acyl  groups  from  which  the  hydroxamic  acids  were  originally  formed. 
Therefore,  in  terms  of  these  radicals  the  ease  of  rearrangement  may  be 
expressed  by  the  following  sequence  :  dibenzylmethyl  >  isopropyl  >  benzyl- 
methyl  >  cyclopropyl. 

Without  further  consideration,  it  can  be  seen  that,  among  these  hydrox- 
amic acid  derivatives,  those  which  contain  the  trimethylene  ring  are  the 
most  stable.  On  the  other  hand,  the  derivatives  of  wobutyr-hydroxamic 
acid  show  a  remarkable  tendency  to  rearrange.  This  is  especially  note- 
worthy, because  of  the  intimate  structural  relationship  which  exists  be- 
tween the  hydroxamic  acids  derived  from  zsobutyric  acid,  and  the  cor- 
responding derivatives  of  cyclopropane-monocarboxylic  acid. 

H3CX  H2Cv 

>CHCONHOH         (a)  |    j>CHCONHOH          (b) 

/  / 


It  may  be  noted  also  that  derivatives  of  acet-hydroxamic  acid8  and  of 
propionhydroxamic  acid9  undergo  rearrangement  with  greater  difficulty 
than  the  corresponding  derivatives  of  250butyr-hydroxamic  acid. 

The  wide  differences  observed  in  the  behavior  of  derivatives  of  benzyl- 
acetic  acid  and  of  dibenzylacetic  acid  seems,  at  first,  to  lead  to  the  assump- 
tion that  the  introduction  of  the  second  benzyl  radical  increases,  in  a 
marked  degree,  the  ease  with  which  corresponding  derivatives  undergo 

8  Jones,  Am.  Chem.  J.,  29,  1  (1898). 

9  The  benzoyl  ester  of  propionhydroxamic  acid  was  prepared  by  Jones  and  Neuf- 
fer,  J.  Am.  Chem,  Soc.,  39,  664  (1917).     It  was  observed  that  the  solid  potassium  salt  of 
this  ester  decomposed  at  120-124°,  the  sodium  salt,  at  86°  and  the  silver  salt,  above 
150°. 


412 

rearrangement.  However,  the  fact  that  derivatives  of  acethydroxamic 
acid8  and  of  propionhydroxamic  acid9  (methylacet-hydroxamic  acid) 
are  not  so  sensitive  to  rearrangement  as  similiar  derivatives  of  isobutyr- 
hydroxamic  acid  (dimethylacet-hydroxamic  acid)  seems  to  force  upon  us 
the  conclusion  that  at  least  a  part  of  the  effect  produced  by  the  introduction 
of  the  second  benzyl  radical  must  be  attributed  to  the  formation  of  an 
iso-  or  branched  chain. 

The  relations  existing  between  chemical  constitution  and  melting 
points  are  presented  in  the  following  table. 

Parent  Hydroxamic  Acids  Benzoyl  Ester  Acetyl  Ester 

°C.  °C.  °c. 

(CH3)2CHCONHOH  (a)    116  148  87 

(C3H5)CHCONHOH  (b)    112  150  108 

(C6H6CH2)2CHCONHOH         (c)    146  147  126     ^ 

It  is  interesting  to  note  that  the  difference  between  the  melting  points  of 
dibenzylacet-hydroxamic  acid  and  of  its  benzoyl  ester  is  only  one  degree. 
A  regularity  is  observed  throughout  the  series,  viz.,  the  melting  points  of 
the  free  hydroxamic  acids  lie  between  those  of  the  higher-melting  benzoyl 
derivatives  and  of  the  lower-melting  acetyl  derivatives. 

III.     Consideration  of  Some  Details. 

The  behavior  of  cyclopropane-monocarboxyl-hydroxamic  acid  and 
its  derivatives  was  of  particular  interest,  since  no  other  hydroxamic  acids 
related  to  cyclic  hydrocarbons  other  than  benzene  and  its  homologs,  or 
hydrocarbons  with  condensed  benzene  nuclei,  have  ever  been  described. 

In  the  preparation  of  this  hydroxamic  acid,  the  method  employed  by 
Perkin10  for  the  preparation  of  the  necessary  ethyl  cyclopropane-mono- 
carboxylate  was  found  to  give  the  best  results.  However,  by  modifying 
Perkin's  procedure  in  several  details,  we  have  been  able  to  obtain  yields 
50%  better  than  those  secured  by  him. 

It  was  observed  that  the  formation  of  dibenzylacet-hydroxamic  acid 
by  the  interaction  of  ethyl  dibenzylacetate  and  free  hydroxylamine 
proceeded  very  slowly,  even  when  the  reaction  mixture  was  kept  between 
60°  and  70°.  The  presence  of  an  extra  mol  of  sodium  methylate  failed 
to  increase  the  speed  of  the  reaction  to  any  great  extent. 

It  was  found  that  this  hydroxamic  acid  could  be  prepared  readily  and 
in  quantity  by  the  action  of  free  hydroxylamine  on  the  acid  chloride 
dissolved  in  benzene.  The  preparation  of  hydroxamic  acids  from  acid 
chlorides  is  a  well  known  method.11  If  water,  generally  employed,  is 
used  as  the  reaction  medium,  a  mixture  of  the  mono-  and  the  dihydroxamic 
acids  always  results.  The  method  suggested  above  for  obtaining  mono- 

10  Perkin,  /.  Chem.  Soc.,  75,  921  (1899). 

11  Lessen,  Ann.,  161,  347  (1872);  175,  285  (1875). 


413 

hydroxamic  acids  gives  yields  almost  quantitative,  with  no  traces  of  the 
di-  acids;  it  has  been  studied  previously  in  this  laboratory.8 

Experimental  Part. 

1.    Hydroxamic  Acids  Related  to  Cyclopropane  Carboxylic  Acid. 

The  Preparation  of  Ethyl  Cyclopropane-l:l-Cyanocarboxylate. — Perkin12  described 
the  preparation  of  cyclopropane-monocarboxylic  acid  in  which  an  alcoholic  solution  of 
sodium  ethyl  malonate  and  ethylene  dibromide  was  digested  under  pressure.  All 
attempts  to  prepare  the  acid  by  this  method  gave  very  small  yields.  Later  Perkin11 
stated  that  when  ethyl  cyano-acetate  was  substituted  for  ethyl  malonate  and  the  mix- 
ture was  digested  at  ordinary  pressure,  he  was  able  to  obtain  a  50%  yield  of  ethyl 
cyclopropane- 1 : 1-cyanocarboxylate.  We  found  the  latter  method  preferable. 

The  changes  made  in  Perkin's  synthesis  consisted  first,  in  the  use  of  an  automatic 
stirrer;  and  second,  hi  the  elimination  of  the  washing  to  which  Perkin  submitted  the 
product  of  reaction  to  remove  colored  materials.  We  find  that  practically  all  the 
color  is  eliminated  by  the  steam  distillation  which  follows. 

To  400  cc.  of  absolute  alcohol  in  a  flask  provided  with  an  automatic  stirrer  and  re- 
flux condenser,  27.4  g.  of  sodium  was  added  in  small  portions.  After  all  of  the  sodium 
had  disappeared  and  the  solution  had  cooled  to  room  temperature,  100  g.  of  ethyl 
cyano-acetate  was  introduced;  this  caused  the  sodium  salt  to  separate.  Then  100  g. 
of  ethylene  dibromide  was  introduced  and  the  mixture  was  heated  to  boiling  on  a  water- 
bath.  The  reaction  mixture  was  stirred  continuously  during  the  entire  operation.  After 
the  product  had  become  neutral  to  litmus,  all  of  the  alcohol  was  distilled  and  sufficient 
water  was  added  to  dissolve  the  sodium  bromide  which  had  separated.  The  mixture  was 
extracted  with  ether  several  times,  the  ether  was  evaporated,  and  the  residual  oil  was 
submitted  to  steam  distillation.  This  distillate  was  saturated  with  ammonium  sulfate 
and  extracted  with  ether  5  or  6  times.  After  the  ether  had  been  dried  over  calcium 
chloride,  it  was  distilled  and  the  oil  was  submitted  to  fractional  distillation.  The 
distillate  which  boiled  between  212°  and  216°,  weighed  64.4  g.  Yield,  76%. 

The  Preparation  of  l:l-Cyclopropane-dicarboxylic  Acid  was  carried  out  according 
to  the  method  described  by  Perkin.  A  portion  of  the  acid,  recrystallized  from  ether, 
gave  a  melting  point  of  134°. 

The  Preparation  of  Cyclopropane-monocarboxylic  Acid. — In  the  preparation  of 
cyclopropane-monocarboxylic  acid  by  dry  distillation  of  this  dibasic  acid,  it  was  found 
that,  by  using  a  lower  temperature  than  that  called  for  by  Perkin  and  by  distilling  the 
monobasic  acid  under  diminished  pressure  as  it  formed,  a  better  yield  was  secured. 

When  36.4  g.  of  the  dibasic  acid  was  distilled  slowly  under  diminished  pressure  and 
the  distillate  was  fractionated,  11.6  g.  of  material  was  obtained.  It  boiled  between  182° 
and  195°.  On  refractionation,  nearly  all  of  this  substance  distilled  between  184°  and 
186  °.  This  was  practically  pure  cyclopropane-monocarboxylic  acid.  A  small  amount 
of  this  compound  can  be  recovered  by  redistillation  of  the  lower  as  well  as  the  higher 
boiling  fractions. 

Attempts  to  prepare  the  ethyl  ester  by  saturation  of  an  alcoholic  solution  of  this 
acid  with  dry  hydrogen  chloride  gave  a  product  which  contained  chlorine.  This  sub- 
stance was  ethyl  chlorobutyrate  produced  by  the  splitting  of  the  trimethylene  ring.14 
In  order  to  obtain  the  ester  of  cyclopropane-monocarboxylic  acid,  the  method  of  Per- 

12  Perkin,  J.   Chem.  Soc.,  47,  807   (1885). 

13Ref.  11,  p.  925. 

14  Boone  and  Perkin,  J.  Chem.  Soc.,  67,  118  (1895);  Ber.,  35,2104  (1902).  Kijner 
J.  Russ.  Chem.  Soc.,  41,  659  (1909).  Tanatar,  Z.  physik.  Chem.,  41,  735  (1902).  Kotz, 
/.  prakt.  Chem.,  [11]  68,  153  (1903).  Barthe,  Bull.  soc.  chim.,  [Ill]  35,  40  (1906). 


414 

kin13  was  followed.  This  required  the  silver  salt.  Since  the  silver  salt  is  extremely 
soluble  in  water  which  contains  small  amounts  of  acid,  of  ammonia,  or  even  of  ammon- 
ium salts,  a  method  for  the  preparation  of  the  pure,  solid  ammonium  salt  was  devised, 
so  that  a  concentrated  solution  of  it  could  be  used  to  prepare  the  silver  salt. 

AMMONIUM  SALT. — A  stream  of  dry  ammonia  gas  was  passed  through  a  solution 
of  the  free  acid  in  anhydrous  ether,  kept  cold  throughout  the  operation  by  means  of  an 
ice-salt  bath.  After  a  short  time,  the  ammonium  salt  began  to  separate  as  a  voluminous 
white  solid.  It  was  collected  and  dried  in  a  desiccator  containing  calcium  oxide  mixed 
with  ammonium  chloride.  The  dry  salt  melted  at  115°.  For  analysis  the  ammonium 
salt  was  digested  with  aqueous  sodium  hydroxide  and  the  ammonia  was  distilled  into 
0.1  N  acid.  The  excess  of  acid  was  titrated  with  a  solution  of  a  standard  base. 

Analysis.  Subs.,  0.2149:  2.12  cc.  of  1  N  acid.  Calc.  for  C4H9O2N:  N,  13.87. 
Found:  13.82. 

The  salt  was  extremely  soluble  in  water  and  in  alcohol  containing  very  small  amounts  of 
water.  It  could  be  kept  for  several  months  in  a  desiccator  containing  a  mixture  of 
calcium  oxide  and  ammonium  chloride. 

SILVER  SALT. — To  25  g.  of  the  ammonium  salt  dissolved  in  a  very  small  amount  of 
water,  the  calculated  amount  of  a  concentrated  solution  of  silver  nitrate  was  added 
slowly,  while  the  solution  was  stirred  vigorously.  The  silver  salt  was  collected  and 
washed  with  cold  water.  Since  this  salt  retained  moisture  very  tenaciously,  it  was 
dried  for  some  time  at  110°,  and  then  analyzed.  The  analysis  confirmed  the  formula 
C4H5O2Ag,  found  by  Perkin. 

The  dry  salt  was  heated  slowly  in  a  test-tube  immersed  in  a  bath  of  sulfuric  acid. 
At  about.  120°,  it  assumed  a  pale  yellow  color  and,  finally,  a  deep  brown  shade  when  the 
bath  had  reached  170°. 

The  Preparation  of  Ethyl  Cyclopropane-monocarboxylate  was  carried  out  by 
refluxing  a  suspension  of  the  silver  salt  in  ether  with  ethyl  iodide  according  to  the  method 
described  by  Perkin. 

H2CX 

A.     Cyclopropane-carboxyl-hydroxamic  acid,        |  y>CHC(O)NHOH. — A  solution 

H2cr 

of  0.96  g.  of  sodium  in  methanol  was  added  to  a  solution  of  2.9  g.  of  hydroxylammonium 
chloride  in  25  cc.  of  methanol.  After  this  mixture  had  been  cooled  and  filtered  to  re- 
move sodium  chloride,  4.2  g.  of  ethyl  cyclopropane-monocarboxylate  was  poured  into 
it.  Finally,  0.84  g.  of  sodium  in  methanol  was  introduced  and  the  mixture  was  allowed 
to  stand  over  night  in  a  warm  place.  After  half  an  hour,  a  drop  of  the  solution  gave  a 
deep  purple  color  when  acidified  and  treated  with  ferric  chloride.  The  next  morning 
dry  carbon  dioxide  was  passed  into  the  solution  thoroughly  cooled,  and  the  sodium 
carbonate  which  formed  was  removed  by  filtration.  After  evaporation  of  the  alcohol, 
a  viscous  semi-solid  mass  resulted. 

This  mass  was  dissolved  in  water  and  treated  with  a  solution  of  copper  acetate. 
A  grass-green  copper  salt  of  the  hydroxamic  acid  was  precipitated ;  it  was  collected,  washed 
thoroughly  with  water  and  dried  over  sulfuric  acid.  When  the  dry  copper  salt  had 
been  pulverized  carefully,  it  was  suspended  in  methanol  and  a  stream  of  dry  hydrogen 
sulfide  was  passed  through  the  suspension.  The  solution  was  filtered  from  copper 
sulfide  and  the  methanol  evaporated. 

The  product  was  a  yellowish  crystalline  material  possessing  an  odor  characteristic 
of  impure  hydroxamic  acids  prepared  from  their  copper  salts  by  this  method.  Upon 
recrystallization  of  it  from  warm  ethyl  acetate,  pure  cyclopropane-monocarboxylic 
hydroxamic  acid  was  obtained;  it  melted  at  124°  with  decomposition.  When  ligroin  is 


415 

added  to  the  ethyl  acetate  solution,  some  of  the  yellow  impurity  is  precipitated  together 
with  a  part  of  the  hydroxamic  acid. 

Analyses.  Subs.,  0.2145:  26.03  cc.  of  N  (22.3°,  754.  mm.).  Calc.  for  C^OjN: 
N,  13.86.  Found:  13.92. 

Subs.,  0.21 :  H2O,  0.1345;  CO2,  0.364.  Calc.  for  C4H7O2N:  C,  47.5;  H,  6.99.  Found: 
C,  47.27;  H,  7.16. 

The  hydroxamic  acid  was  soluble  in  water,  in  methanol,  in  ethyl  alcohol,  and  in 
hot  ethyl  acetate.  It  was  only  slightly  soluble  in  ether  and  was  insoluble  in  ligroin. 

B.  Benzoyl  Ester  of  Cyclopropane-Carboxyl-hydroxamic  Acid,  C3HSC(O)NHO- 
COC6H5. — When  an  aqueous  solution  of  the  sodium  salt  of  (A)  was  shaken  with  benzoyl 
chloride,  the  benzoyl  ester  mixed  with  benzoyl  chloride  and  benzoic  acid  separated  as  a 
white  mass.  The  product  was  collected  and  pressed  on  a  porous  plate  and,  when  dry, 
was  extracted  repeatedly  with  boiling  ligroin  and  recrystallized  from  hot  ethyl  alcohol 
to  which  water  was  added  until  a  slight  turbidity  occurred.  As  the  solution  cooled, 
pure  benzoyl  ester  separated  in  the  form  of  white  needles  which  were  collected,  washed 
with  dilute  alcohol  and  dried.  It  melted  at  150°. 

Analyses.  Subs.,  0.4931;  30.4  cc.  of  N  (24.7°,  741  mm.).  Calc.  for  CiiHuO3N: 
N,  6.83.  Found:  6.9. 

Subs.,  0.1543:  H2O,  0.0772;  CO2,  0.3643.  Calc.  for  CUHUO,N:  C,  64.36;  H,  5.41. 
Found:  C,  64.38;  H,  5.59. 

It  is  soluble  in  ether  and  in  ethyl  alcohol,  but  only  slightly  soluble  in  ligroin  and  is 
insoluble  in  water. 

POTASSIUM  SALT  OF  (B). — A  solution  of  0.4  g.  of.  the  benzoyl  ester  in  absolute 
alcohol  was  cooled  by  means  of  an  ice-salt  bath,  and  treated  with  the  calculated  amount 
of  potassium  ethylate.  The  potassium  salt,  a  white  solid,  was  collected,  washed  with 
anhydrous  ether  and  dried  in  vacua  over  sulfuric  acid.  Anhydrous  ether  added  to  the 
filtrate  precipitated  more  of  the  potassium  salt.  The  dry  salt  puffed  when  it  was  heated 
to  103°.  An  isocyanate  odor  was  detected  and  potassium  benzoate  was  formed. 

Analysis.  Subs.,  0.172:  K2SO4,  0.0599.  Calc.  for  CnH10O3NK:  K,  16.07.  Found: 
15.64. 

A  clear  aqueous  solution  of  1.2  g.  of  the  potassium  salt,  when  heated  to  90°,  gave  a 
white  solid  product.  This  was  collected  and  washed  with  water.  A  portion  of  the  fil- 
trate was  made  slightly  acid  and,  upon  the  addition  of  a  solution  of  ferric  chloride,  an 
intense  purple  coloration  was  produced,  which  showed  that  a  part  of  the  benzoyl  ester, 
formed  by  hydrolysis  of  the  salt,  had  been  hydrolyzed  still  further  to  yield  some  mono- 
hydroxamic  acid.  When  the  filtrate  was  acidified,  carbon  dioxide  was  evolved  and  0.3  g. 
of  benzoic  acid  was  precipitated. 

The  solid  product  was  extracted  with  a  solution  of  sodium  hydroxide,  and  from  this 
solution  0.1  g.  of  the  benzoyl  ester  was  recovered.  That  portion  of  the  solid  which  was 
insoluble  in  alkalies  resembled  the  expected  symmetrical  di-cyclopropyl  urea.  It  was 
insoluble  in  water,  but  very  soluble  in  alcohol  and  in  ether.  However,  the  quantity 
obtained  was  too  small  to  permit  of  complete  purification  and  analysis.  The  partially 
purified  solid  melted  between  172°  and  178°. 

When  the  dry  potassium  salt  was  heated  until  decomposition  ensued,  it  gave  a 
low-boiling  oil,  evidently  cyclopropyl  isocyanate.  This  oil  was  distilled  and  the  vapor 
was  passed  into  a  small  amount  of  aniline.  The  excess  of  aniline  was  removed  by  ex- 
traction with  acid  and  the  solid  residue  was  crystallized  from  hot  ether  and  ligroin. 
It  melted  at  151°,  and  its  properties  corresponded  with  those  of  phenyl-cyclopropyl 
urea,  C«H6NHCONH(C«H6),  described  by  Kijner.15 

15  Kijner,  J.  Russ.  Chem.,  47.  304-317  (1905). 


416 

SODIUM  SALT  OP  (B). — A  solution  of  0.5  g.  of  the  benzoyl  ester  in  cold  absolute 
alcohol  was  treated  with  the  calculated  amount  of  sodium  ethylate.  The  addition  of 
more  than  6  volumes  of  anhydrous  ether  was  required  to  precipitate  the  sodium  salt. 
This  was  collected  and  dried  in  vacuo  over  sulfuric  acid.  The  dry  salt  puffed  at  143°; 
a  deposit  of  sodium  benzoate  remained  in  the  test-tube  and  an  isocyanate  odor  was  no- 
ticed. An  aqueous  solution  of  the  sodium  salt  behaved  in  a  manner  similar  to  that 
of  the  potassium  salt  described  above. 

SILVER  SALT  OF  (B). — A  solution  of  silver  nitrate  was  added  to  a  clear  aqueous 
solution  of  the  potassium  salt.  The  white  silver  salt  was  collected,  washed  with  water, 
then  with  alcohol,  and  finally  with  ether. 

Analysis.  Subs.,  0.2468:  Ag,  0.0843.  Calc.  for  CnH,0O«NAg:  Ag,  34.57.  Found: 
34.16. 

When  the  dry  salt  was  heated  above  200°,  it  decomposed  and  gave  a  strong  iso- 
cyanate odor. 

C.  Acetyl  Ester  of  Cyclopropane-monocarboxyl-hydroxamic  acid,  (C8H5)CONHO- 
COCHj... — A  slight  excess  of  acetic  anhydride  was  added  to  1  g.  of  cyclopropane-mono- 
carboxyl-hydroxamic  acid.  When  the  mixture  was  warmed  gently,  it  became  a  clear 
liquid  which  solidified  almost  immediately.  As  the  temperature  was  raised  slightly, 
the  product  became  liquid  once  more.  This  solution  was  stirred  until  a  test  portion 
failed  to  give  a  purple  coloration  with  ferric  chloride.  The  excess  of  acetic  anhydride 
and  of  acetic  acid  was  removed  by  placing  the  product  in  a  vacuum  desiccator  over 
solid  potassium  hydroxide. 

The  ester,  recrystallized  from  warm  ether,  formed  very  fine  white  needles  so  closely 
matted  together  that  the  product  retained  the  shape  of  the  filter  paper  upon  which  it 
was  collected.  Dried  in  vacuo  over  sulfuric  acid,  it  melted  at  108°. 

Analysis.  Subs.,  0.2783:  24.2  cc.  of  N  (23°,  748  mm.).  Calc.  for  C6H9O3N:  N, 
9.78.  Found:  9.87. 

It  was  soluble  in  water,  in  alcohol,  in  acetone,  in  ethyl  acetate,  and  in  hot  ether, 
but  only  slightly  soluble  in  cold  ether,  and  insoluble  in  ligroin. 

POTASSIUM  SALT  OP  (C). — A  cold  solution  of  0.5  g.  of  the  acetyl  ester  in  ab- 
solute alcohol  was  treated  with  the  calculated  amount  of  potassium  ethylate;  upon  the 
addition  of  anhydrous  ether,  the  potassium  salt  was  obtained  as  a  white  precipitate. 
This  was  separated,  washed  with  ether,  and  dried  in  vacuo  over  sulfuric  acid.  The  dry 
salt  puffed  when  immersed  in  a  bath  previously  heated  to  155°. 

Analysis.  Subs.,  0.0891:  K2SO4,  0.0423.  Calc.  for  C6H8O3NK:  K,  21.58.  Found: 
21.32. 

2.    Hydroxamic  Acids  Related  to  Dibenzylacetic  Acid. 

The  preparation  of  Dibenzylacetyl  Chloride,  (CeHsCHa^CHCOCl.— Ethyl  di- 
benzyl-aceto-acetate  was  prepared  according  to  the  method  of  Merz  and  Weith16  and 
also  that  of  F.  Seserrnann.17  Both  methods  gave  good  results.  This  compound  was 
made  to  undergo  the  "acid  splitting,"  as  described  by  Deikmann  and  Kron,ls  viz.,  by 
refluxing  it  with  sodium  ethylate.  The  ethyl  dibenzylacetate,  thus  produced,  was 
saponified  with  alcoholic  potash.  One  crystallization  of  the  product  from  hot  ligroin 
gave  dibenzylacetic  acid  which  melted  at  89°.  Its  properties  corresponded  with  the 
known  properties  of  dibenzylacetic  acid. 

When  10  g.  of  dibenzylacetic  acid  was  treated  with  an  excess  of  thionyl  chloride 

16  Merz  and  Weith,  Ber.,  10,  759  (1877). 

17  Sesermann,    ibid.,    6,    1086    (1873). 

18  Deikmann  and  Kron,  ibid.,  41,  1266  (1908). 


417 

and  the  mixture  was  warmed,  sulfur  dioxide  and  hydrogen  chloride  were  evolved  and 
the  reaction  mixture  became  liquid.  After  this  material  had  been  refluxed  for  a  short 
time  the  excess  of  thionyl  chloride  was  distilled  and  the  residual  oil  was  submitted  to- 
fractional  distillation  under  diminished  pressure.  When  the  last  traces  of  thionyl 
chloride  had  been  removed,  the  thermometer  rose  rapidly  to  203°,  and  the  entire  product 
distilled  between  203°  and  205°  under  17  mm.  It  was  a  yellow  oil  soluble  in  benzene 
and  insoluble  in  water.  It  was  hydrolyzed  slowly  in  moist  air. 

D.  Dibenzylacet-hydroxamic    Acid,    (C6H6CH2)2CHCONHOH.     METHOD   I.— 
A  methanol  solution  containing  5.25  g.  of  hydroxylammonium  chloride  was  treated  with 
1.7  g.  of  sodium  in  methanol.     Sodium  chloride  was  removed  and  the  filtrate  was  treated 
with  20  g.  of  ethyl  dibenzylacetate.     These  materials  were  thoroughly  mixed  and  a 
solution  of  1.5  g.  of  sodium  in  methanol  was  poured  in.     After  several  hours  at  room 
temperature,  the  mixture  gave  no  test  with  ferric  chloride  for  a  hydroxamic  acid.     At 
the  end  of  18  hours,  only  a  slight  coloration  was  produced  when  ferric  chloride  was 
added  to  an  acidified  test  portion  of  the  reaction  mixture.     So  the  solution  was  warm 
several  hours  to  60°  or  70°  and  the  methanol  allowed  to  evaporate. 

This  gave  a  white  solid  which  was  dissolved  in  a  cold  solution  of  sodium  hydroxide 
and  extracted  with  ether  to  remove  any  unchanged  ester.  When  the  solution  was 
acidified,  a  solid  white  substance  separated.  This  was  collected,  washed  with  water  and 
pressed  on  a  porous  plate.  The  dry  solid  was  extracted  repeatedly  with  hot  ligroin  to- 
remove  any  dibenzylacetic  acid,  and  the  undissolved  dibenzylacet-hydroxamic  acid  was 
recrystallized  from  hot  benzene.  It  melted  at  146°.  The  yield  was  very  small. 

Analysis.  Subs.,  0.2718:  13.16  ccr.  of  N  (18°,  745.3  mm.).  Calc.  for  Ci6Gi7O2N :  N^ 
5.49.  Found:  5.57. 

It  was  soluble  in  hot  benzene,  in  alcohol,  in  alkalies  and  in  ethyl  acetate,  but  only 
slightly  soluble  in  cold  benzene  and  in  ether,  and  insoluble  in  water  or  in  ligroin.  An 
alcoholic  solution,  made  faintly  acid  with  acetic  acid,  gave  a  grass-green  copper  salt 
when  an  alcoholic  solution  of  copper  acetate  was  added.  An  alcoholic  solution  of  the 
hydroxamic  acid  reduced  a  solution  of  silver  nitrate  slowly. 

METHOD  II.— The  following  method  gave  dibenzylacet-hydroxamic  acid  practically 
quantitatively.  To  a  solution  of  10  g.  of  dibenzylacetyl  chloride  in  dry  benzene,  slightly 
more  than  the  calculated  amount  of  free  hydroxylamine  was  added.  When  the  mixture 
was  agitated,  it  became  warm  rapidly,  so  that  it  was  necessary  to  cool  the  flask  with 
tap  water.  Hydroxylammonium  chloride  and  some  of  the  hydroxamic  acid  separated 
as  a  white  precipitate,  while  the  excess  of  free  hydroxylamine  formed  a  gum  which  ad- 
hered to  the  side  of  the  containing  vessel.  When  the  solution  was  heated  to  boiling,  filtered 
while  hot,  and  then  cooled,  pure  dibenzylacet-hydroxamic  acid  separated.  Its  proper- 
ties corresponded  in  every  way  with  those  described  above. 

E.  Benzoyl   Ester  of  Dibenzylacet-hydroxamic  Acid,    (CeH^CH^CHCONHO- 
COC6H5. — When  an  aqueous  solution  of  10  g.  of  dibenzylacet-hydroxamic  acid  with 
the  calculated  amount  of  alkali  was  cooled  and  shaken  with  benzoyl  chloride,  this 
ester  separated  as  a  white  solid.     This  material  collected  and  pressed  on  a  porous  plate 
The  dry  product,  extracted  with  hot  ligroin  several  times  to  remove  unused  benzoyl 
chloride  and  benzoic  acid,  was  crystallized  from  hot  alcohol  by  addition  of  hot  water 
until  the  solution  became  faintly  turbid.     As  this  mixture  cooled,  pure  benzoyl  ester 
of  dibenzylacet-hydroxamic  acid  separated  in  the  form  of  white  needles  which  were 
collected,  washed  with  cold,  very  dilute  alcohol  and  dried.     It  melted  at  147°. 

Analysis.  Subs.,  0.3068:  10.2  cc.  of  N  (20°,  746  mm.).  Calc.  for  CwHziOaN: 
N,  3.90.  Found:  3.80. 

The  ester  was  soluble  in  alcohol;  it  was  only  slightly  soluble  in  ether  and  was  insol- 
uble in  water. 


418 

POTASSIUM  SALT  otf  (E). — Five-tenths  g.  of  the  benzoyl  ester  was  dissolved  in 
cold  absolute  alcohol  and  treated  with  the  calculated  amount  of  potassium  ethylate, 
upon  the  addition  of  over  10  volumes  of  anhydrous  ether,  only  a  very  small  amount  of 
the  solid  salt  was  precipitated.  This  was  collected  and  dried  in  vacua  over  sulfuric 
acid.  When  the  salt  was  heated  on  a  spatula,  it  decomposed  to  give  a  vapor  with  an 
isocyanate  odor,  and  potassium  benzoate.  When  the  salt  was  treated  with  cold  water, 
an  insoluble  part  always  remained.  This  was  washed  with  alkali  and  water.  After 
it  was  crystallized  from  dil.  alcohol,  its  properties  corresponded  with  those  of  the  synthe- 
sized yyw.bi-dibenzylmethyl  urea  described  below.  When  the  potassium  salt  was 
dissolved  in  water  at  room  temperature,  a  turbidity  appeared  immediately,  and  the 
corresponding  disubstituted  urea  began  to  separate  at  once.  Application  of  heat  in- 
creased the  speed  of  this  reaction. 

An  attempt  was  made  to  prepare  the  sodium  salt  of  (E)  by  the  method  used  above 
in  the  preparation  of  the  potassium  salt  No  precipitate  was  produced,  even  when 
several  hundred  cubic  centimeters  of  anhydrous  ether  was  added.  An  aqueous  extrac- 
tion of  this  alcohol-ether  solution  of  the  sodium  salt  soon  gave  the  urea. 

SILVER  SALT  OP  (E) . — A  solution  of  1  g.  of  the  benzoyl  ester  in  absolute  alcohol 
was  cooled  to  —10°,  and  treated  with  slightly  less  than  the  calculated  amount  of  potas- 
sium ethylate.  Then  an  alcoholic  solution  containing  slightly  less  than  the  calculated 
amount  of  silver  nitrate  was  added  to  this  cold  solution.  Only  a  small  amount  of  a 
very  light,  fluffy  precipitate  resulted.  However,  upon  the  addition  of  anhydrous  ether, 
the  silver  salt  was  obtained  in  quantity.  This  was  collected,  washed  with  absolute 
alcohol  and  with  water,  then  again  with  absolute  alcohol  and  finally  with  anhydrous 
ether.  This  silver  salt,  dried  in  vacuo  over  sulfuric  acid,  puffed  at  143°,  to  give  an  oil 
which  distilled  into  the  cooler  portions  of  the  tube,  while  silver  benzoate  was  left  as 
solid.  Evidently,  this  oil  was  dibenzylmethyl  isocyanate,  for  upon  treating  it  with 
warm  water  the  corresponding  urea  was  produced. 

Analysis.  Subs.,  0.1860:  Ag,  0.0428.  Calc.  for  C23H2oO3NAg:  Ag,  23.14:  Found: 
23.01. 

F.  Acetyl  Ester  of  Dibenzylacet-hydroxamic  Acid,  (C6H6CH2).CHCON(H)- 
OCOCH3. — Five-tenths  g.  of  pure  dibenzylacet-hydroxamic  acid  and  a  slight  excess 
of  acetic  anhydride  were  heated  on  a  water-bath  until  a  test  portion  failed  to  give  a 
violet  coloration  with  ferric  chloride.  As  the  product  became  cool,  it  solidified.  It  was 
kept  over  soda-lime  in  a  vacuum  desiccator  until  all  traces  of  acetic  acid  and  acetic 
anhydride  had  disappeared,  and  then  recrystallized  from  hot  benzene.  It  melted  at 
126°. 

Analysis.  Subs.,  0.4194:  18.4  cc.  of  N  (19°,  741  mm.).  Calc.  for  Ci6Hi2O3N: 
N,  4.71.  Found:  5.00. 

The  ester  was  soluble  in  hot  benzene,  in  alcohol,  in  ethyl  acetate  and  in  acetone. 
It  was  only  slightly  soluble  in  ether  and  was  insoluble  in  water  and  in  ligroin.  When  a 
hot,  saturated  solution  of  the  ester  in  absolute  alcohol  was  cooled  slowly,  large,  clear, 
square  plates  were  obtained. 

An  attempt  to  prepare  the  potassium  salt  by  dissolving  1.2  g.  of  (F)  in  cold 
absolute  alcohol  and  adding  to  it  the  calculated  amount  of  potassium  ethylate  failed 
to  give  any  precipitate,  even  when  more  than  200  cc.  of  anhydrous  ether  was  introduced. 
Traces  of  moisture  absorbed  during  manipulation  evidently  effected  rearrangement  of 
some  of  the  salt,  for  on  evaporation  of  a  part  of  the  alcohol-ether  solution  in  vacuo 
over  sulfuric  acid  some  syw.bi-dibenzylmethyl  urea  was  obtained.  In  the  preparation 
of  the  sodium  salt,  difficulties  similar  to  those  described  in  the  preparation  of  the  potas- 
sium salt  were  encountered. 

SILVER   SALT   OF    (F). — Five-tenths  g.  of  the  acetyl  ester  was  dissolved  in  ab- 


419 

solute  alcohol.  To  this  solution,  cooled  to  — 12°,  slightly  less  than  the  calculated  amount 
of  an  alcoholic  solution  of  silver  nitrate  was  added.  When  the  walls  of  the  containing 
vessel  were  scratched  with  a  stirring  rod,  a  white  silver  salt  was  precipitated.  This 
was  collected,  washed  with  absolute  alcohol,  then  with  water,  again  with  absolute 
alcohol,  and  finally  with  anhydrous  ether. 

The  dry  salt,  heated  slowly,  turned  brown  at  125°,  and  suddenly  black  at  145°. 
When  it  was  heated  on  a  spatula,  an  isocyanate  odor  was  detected.  On  exposure  to 
light  it  turned  purple.  It  was  insoluble  in  water,  in  alcohol  and  in  ether,  but  was 
soluble  in  ammonium  hydroxide.  A  suspension  of  the  salt  in  cold  water  containing  the 
calculated  amount  of  potassium  bromide  was  shaken  thoroughly  and  filtered  from  the 
silver  bromide  formed.  When  this  solution  was  warmed,  it  gave  a  precipitate  of  sym. 
bi-dibenzylmethyl  urea. 

In  order  to  prepare  a  sample  of  this  urea  for  comparison,  dibenzyl  ketone  made  by 
the  dry  distillation  of  the  calcium  salt  of  phenylacetic  acid,  as  described  by  Apitzsch,19 
was  converted  into  the  oxime,  from  which  dibenzylmethyl  amine  was  prepared  according 
to  the  method  described  by  Noyes.20  The  urea  was  synthesized  from  this  amine  as 
follows. 

G.  Sym.-bi-dibenzylmethyl  Urea,  ((QHsCHs^CHNKQaCO.— Phosgene  was  passed 
into  a  dry  ether  solution  of  the  amine.  Bi-dibenzylmethyl  urea  and  dibenzyl-carbamine 
hydrochloride  were  precipitated  as  a  white  solid  which  was  collected  and  extracted 
several  times  with  boiling  water  in  order  to  dissolve  the  amine  hydrochloride.  The 
crude  urea,  left  after  extraction,  was  recrystallized  from  hot  alcohol  and  hot  water. 
The  pure  urea  separated  in  the  form  ef  small  white  needles  which  melted  at  159°. 

Analysis.  Subs.,  0.1407:  7.26  cc.  of  N  (18°,  748  mm.).  Calc.  for  C3iHKON2 :  N, 
6.25.  Found:  6.25. 

It  was  soluble  in  ethyl  acetate,  in  acetone,  in  alcohol,  and  in  benzene,  but  was 
insoluble  in  water,  in  ether  and  in  ligroin.  A  melting  point  was  taken  of  a  mixture  of 
the  urea  synthesized  above  and  of  that  formed  as  a  product  of  the  rearrangement  of 
the  different  salts  of  the  esters  of  dibenzylacet-hydroxamic  acid.  This  melting  point 
of  the  mixture  was  159°. 

3.     Experiments  with  Tribenzy  1m ethyl  Chloride. 

Tribenzyl  carbinol  was  made  from  ethyl  phenylacetate  by  the  Grignard  reaction 
according  to  Klages  and  Heilmann.21  A  considerable  quantity  of  dibenzyl  was  obtained 
as  a  by-product. 

H.  Tribenzylmethyl  Chloride,  (CeHsCHOsCCl. — To  10  g.  of  the  carbinol,  15  cc. 
of  acetyl  chloride  was  added  and  the  mixture  was  refluxed  for  hours.  A  short  time 
after  the  refluxing  was  commenced  the  undissolved  carbinol  passed  into  solution.  When 
the  solution  was  allowed  to  cool  very  slowly,  resets  of  colorless  needles  of  tribenzyl- 
methyl  chloride  separated.  These  needles  were  collected  and  washed  thoroughly  with 
anhydrous  ether  to  remove  acetyl  chloride,  acetic  acid,  and  any  unchanged  carbinol. 
After  the  chloride  had  been  dried  over  calcium  chloride,  it  melted  at  about  173° 
with  decomposition. 

Analysis.  Subs.,22  1601:  4.15  cc.  of  0. 12094  N  NaSCN.  Calc.  for  CaH21Cl:  Cl, 
11.06.  Found:  11.16. 


19  Apitzsch,    Ber.,   36,    1428    (1904). 
?0  Noyes,  Am.  Chem.  J.,  14,  226  (1892). 
21  Klages  and  Heilmann,   Ber.,  37,   1456    (1904). 

-~  An  analysis  of  this  chloride  was  made  by  heating  a  sample  of  it  with  10  g.  of 
in  a  Parr  sulfur  bomb.     The  usual  Volhard  method  was  employed  to  determine 
the  chlorine. 


420 

It  was  soluble  in  hot  benzene  and  in  hot  acetone.  It  was  only  very  slightly  soluble 
in  ligroin,  in  cold  benzene  and  in  cold  acetone.  It  was  insoluble  in  water,  in  alcohol, 
and  in  ether. 

Because  of  the  ease  of  decomposition,  the  preparation  of  the  chloride  through  the 
action  of  phosphorus  trichloride  or  pentachloride  on  the  carbinol  was  unsuccessful. 
The  chloride  could  be  recrystallized  from  acetyl  chloride,  but  recrystallization  from 
anhydrous  benzene  always  lowered  the  melting  point.  It  was  very  slowly  decomposed 
by  boiling  water  or  by  a  boiling  10%  solution  of  potassium  hydroxide. 

When  the  chloride  was  heated  slightly  above  its  melting  point  until  the  evolution 
of  hydrogen  chloride  ceased,  an  oil  formed  which  would  not  solidify  when  it  was  cooled 
in  an  ice-salt  bath.  This  oil  was  soluble  in  ether,  and  an  anhydrous  ether  solution  of  it 
•decolorized  bromine  fairly  rapidly.  This  seemed  to  indicate  that  the  oil  contained  a 
compound  of  an  unsaturated  olefin  nature,  most  likely  dibenzyl-cinnamene,  CeH5CH  = 
C(CH2C6H5)2.  This  product  was  not  investigated  further. 

Behavior  of  the  Chloride  toward  Magnesium  (Grignard  Reaction). — An  anhydrous 
ether  solution  of  tribenzylmethyl  chloride  mixed  with  magnesium  was  refluxed  for  8 
hours.  No  evidence  of  a  reaction  could  be  detected,  even  when  iodine  was  added. 
Methyl  iodide  also  failed  to  start  the  reaction. 

Because  of  the  insolubility  of  the  chloride  in  ether,  anhydrous  benzene  was  employed 
as  the  reaction  medium.  Iodine,  methyl  iodide,  and  aniline  were  used  as  "primers," 
and  the  solution  was  refluxed  for  3  days  without  effect.  When  this  benzene  solution 
was  cooled,  needles  of  the  chloride  separated.  These  crystals  melted  at  about  165°, 
instead  of  173°,  the  melting  point  of  the  pure  chloride. 

4.    Hydroxamic  Acids  Related  to  Isobutyric  Acids. 

I.  Isobutyr-hydroxamic  Acid  or  Dimethylacet-hydroxamic  Acid,  (CH3)2CHC(O)- 
NHOH. — Isobutyr-hydroxamic  acid  was  made  by  two  methods. 

METHOD  I. — A  solution  of  4.9  g.  of  sodium  in  methanol  was  poured  into  a  methanol 
solution  of  7.85  g.  of  hydroxylammonium  chloride  and  the  mixture  cooled  to  — 12°. 
The  sodium  chloride  was  removed  and  11.5  g.  of  methyl  wobutyrate  was  added  to  the 
filtrate.  After  these  substances  were  thoroughly  mixed,  4.8  g.  of  sodium  in  methanol 
was  introduced  and  the  solution  allowed  to  stand  at  room  temperature  overnight. 
When  a  test  portion  of  the  reaction  mixture,  removed  immediately  after  the  last  addition 
of  sodium  methylate,  was  acidified  it  gave  a  pronounced  color  with  ferric  chloride. 
After  12  hours,  a  stream  of  dry  carbon  dioxide  was  passed  through  the  solution  to 
precipitate  sodium  carbonate.  The  product,  thoroughly  cooled  in  an  ice-salt  bath, 
was  filtered  from  the  sodium  carbonate  and  the  methanol  was  evaporated. 

The  solid,  which  consisted  of  sodium  chloride  and  of  wobutyr-hydroxamic  acid, 
was  dissolved  in  water  made  faintly  acid  with  acetic  acid.  Upon  the  addition  of  an 
aqueous  solution  of  copper  acetate,  a  grass-green  copper  salt  of  the  hydroxamic  acid 
was  precipitated.  This  salt  was  collected,  washed  with  water,  then  with  alcohol  and 
finally  with  ether.  After  it  had  been  dried  thoroughly  and  pulverized,  it  was  suspended 
in  methanol  and  a  stream  of  dry  hydrogen  sulfide  was  passed  through  the  mixture. 
When  the  copper  sulfide  had  been  removed  by  filtration,  and  the  ether  evaporated, 
wobutyr-hydroxamic  acid  was  obtained.  Crystallized  from  ethyl  acetate  and  ligroin, 
or  from  benzene,  it  melted  at  116°. 

Analysis.  Subs.,  0.0857:  10.35cc.of  N  (21°,  743  mm.).  Calc.  for  C4H6O2N :  N, 
13.60.  Found:  13.73. 

It  was  soluble  in  ether,  in  alcohol,  in  water,  in  acetone,  in  hot  ethyl  acetate,  and 
in  hot  benzene.  It  was  insoluble  in  ligroin. 

METHOD  II. — /^/butyric  acid  was  refluxed  a  short  time  with  thionyl  chloride  and 
the  excess  of  this  reagent  was  distilled  /sobutyryl  chloride  was  obtained  by  fractionat- 


421 

ing  the  resulting  oil.  An  anhydrous  benzene  solution  of  the  acid  chloride,  kept  thoroughly 
cooled  by  immersion  in  an  ice-bath,  was  agitated  vigorously  with  a  slight  excess  of 
free  hydroxylamine.  When  the  reaction  was  complete,  the  solution  was  heated  and 
filtered  while  hot.  As  the  filtrate  cooled,  wobutyr-hydroxamic  acid  separated.  It  was 
recrystallized  from  ethyl  acetate  and  ligroin.  For  the  preparation  of  this  particular 
hydroxamic  acid,  Method  I  was  found  to  be  preferable. 

J.  Benzoyl  Ester  of  Isobutyr-hydroxamic  Acid,  (CHj^CHCONHOCOCeHs.— 
This  ester  was  prepared  in  two  ways. 

METHOD  I. — /sobutyr-hydroxamic  acid  was  treated  with  benzoyl  chloride  according 
to  the  Schotten-Baumann  method.  The  precipitate  was  removed  and  pressed  on  a 
porous  plate.  When  this  crude  material  was  extracted  several  times  with  hot  ligroin 
and  crystallized  from  a  mixture  of  hot  alcohol  and  hot  water,  the  benzoyl  ester  of  iso- 
butyr-hydroxamic  acid  separated  in  the  form  of  white  needles;  m.  p.  148°. 

METHOD  II. — /sobutyr-hydroxamic  acid  was  warmed  on  a  water-bath  with  a  slight 
excess  of  benzoic  anhydride,  until  a  test  portion  of  the  reaction  mixture  failed  to  give  a 
violet  color  when  treated  with  a  solution  of  ferric  chloride.  The  product  solidified  when 
cold.  This  mass  was  broken  up,  extracted  several  times  with  hot  ligroin,  and  recrystal- 
lized from  a  mixture  of  hot  alcohol  and  hot  water.  It  formed  white  needles  which  melted 
at  148°. 

Analysis.  Subs.,  0.2301:  14.01  cc.  of  N  (24.3°,  744  mm.).  Calc.  for  CnH13O3N: 
N,  6.77.  Found:  6.85. 

The  benzoyl  ester  was  soluble  in  alcohol,  in  ethyl  acetate,  and  in  hot  benzene.  It 
was  slightly  soluble  in  ether,  and  was  insoluble  in  water  and  in  ligroin. 

POTASSIUM  SALT  OP  (J). — A  solution  of  0.5  g.  of  the  benzoyl  ester  of  iso- 
butyr-hydroxamic  acid  in  absolute  alcohol  was  immersed  in  an  ice-salt  bath,  and  0.094  g. 
of  sodium  dissolved  in  absolute  alcohol  was  added.  Anhydrous  ether  caused  a  white 
precipitate  to  form  which  was  collected,  washed  with  anhydrous  ether  and  dried  over  sul- 
f  uric  acid.  When  the  dry  salt  was  heated  slowly  to  200°,  no  decomposition  occurred ;  but 
when  a  portion  in  a  test-tube  was  quickly  thrust  into  a  bath  at  150°  it  puffed;  an  iso- 
cyanate  odor  was  noticed  and  a  deposit  of  potassium  benzoate  remained  in  the  tube. 

The  salt  obtained  above  was  thought  to  be  impure,  so  it  was  prepared  a  second  time. 
In  the  second  preparation,  slightly  less  than  the  calculated  amount  of  potassium  ethylate 
was  used  and  the  salt  was  washed  more  thoroughly  with  anhydrous  ether.  It  was 
placed  over  sulfuric  acid  in  a  desiccator  immediately  and  the  desiccator  evacuated. 
In  about  20  minutes,  the  salt  decomposed  spontaneously  with  such  violence  as  to  scatter 
potassium  benzoate  throughout  the  desiccator.  When  the  desiccator  was  opened,  it 
was  found  to  be  filled  with  the  vapor  of  the  isocyanate. 

An  aqueous  solution  of  the  potassium  salt  was  warmed  to  50°  for  some  time.  The 
light,  oily  layer  which  separated  possessed  a  strong  isocyanate  odor.  This  solution, 
allowed  to  stand  for  several  hours  at  room  temperature,  finally  deposited  a  mass  of  fine 
white  needles.  These  were  collected,  washed  with  alkali  to  remove  any  unchanged  es- 
ter and  any  traces  of  wobutyr-hydroxamic  acid  produced  by  hydrolysis.  Its  properties 
were  like  those  of  the  symmetrical  di-wopropyl  urea  described  by  Hofmann.23 

SODIUM  SALT  OP  (J). — To  0.5  g.  of  the  benzoyl  ester  dissolved  in  absolute 
alcohol  and  cooled  to  —10°,  0.055  g.  of  sodium  dissolved  in  absolute  alcohol  was  intro- 
duced. Upon  the  addition  of  anhydrous  ether,  the  white  sodium  salt  was  precipitated. 
This  was  collected,  washed  with  ether  and  dried  over  sulfuric  acid.  At  75°  it  puffed, 
gave  an  isocyanate  odor  and  left  sodium  benzoate  in  the  tube.  An  aqueous  solution 
of  the  sodium  salt  behaved  in  a  manner  analogous  to  that  of  the  potassium  salt  de- 
scribed above. 


23  Hofmann,  Ber.,  15,  756  (1882). 


422 

SILVER  SALT  OP  (J). — An  aqueous  solution  of  the  potassium  or  sodium  salt 
was  treated  with  an  aqueous  solution  of  silver  nitrate.  The  white  silver  salt  was  collected, 
washed  with  water,  then  with  a  little  alcohol,  and  finally  with  ether.  When  the  dry 
silver  salt  was  heated  slowly  in  a  test-tube,  it  turned  brown  at  180°.  When  the  bath 
has  reached  200°  the  sample  was  removed  and  passed  through  a  free  flame,  whereupon 
it  puffed  vigorously;  an  isocyanate  odor  was  noticed  and  silver  benzoate  remained  in 
the  tube.  The  silver  salt  prepared  from  the  potassium  salt  gave  the  following  analyt- 
ical results. 

Analysis.  Subs.,  0.0460:  Ag,  0.0158.  Calc.  for  CnHi2O3NAg:  Ag,  34.35.  Found: 
34.35. 

K.  Acetyl  Ester  of  Isobutyr-hydroxamic  Acid,  (CH3)2CHCONHOCOCH3.— 
A  mixture  of  1  g.  of  the  hydroxamic  acid  and  1  cc.  of  acetic  anhydride  was  warmed  on 
a  water-bath  until  a  test  portion  failed  to  give  a  ferric  chloride  reaction.  As  the  mix- 
ture became  cool,  the  product  solidified.  The  mass  was  broken  up  and  placed  in  a 
vacuum  desiccator  over  sodium  hydroxide,  where  it  remained  until  all  the  acetic  an- 
hydride had  been  removed.  After  it  was  recrystallized  from  hot  benzene  and  ligroin, 
it  melted  at  87°. 

Analysis.  Subs.,  0.2004:  17.45  cc.  of  N  (21°,  748  mm.).  Calc.  for  C6HUO3N: 
N,  9.65.  Found:  9.95. 

The  acetyl  ester  was  soluble  in  water,  in  hot  ether,  in  hot  benzene  and  in  alcohol, 
but  was  insoluble  in  ligroin. 

POTASSIUM  SALT  OF  (K).— Upon  the  addition  of  ether  to  a  cold  absolute 
alcoholic  solution  of  the  acetyl  ester  of  wobutyr-hydroxamic  acid  to  which  the  calculated 
amount  of  potassium  ethylate  had  been  added,  a  white  precipitate  of  the  potassium 
salt  was  obtained.  This  was  filtered,  washed  with  anhydrous  ether  and  dried.  The 
potassium  salt  was  very  deliquescent;  it  absorbed  sufficient  moisture  from  the  air  to 
effect  its  solution  in  a  very  short  time.  A  sample  of  the  dry  salt  which  had  stood  over 
sulfuric  acid  for  30  minutes,  puffed  when  heated  to  53°,  and  gave  an  isocyanate  odor. 
After  it  had  remained  in  the  desiccator  for  several  hours,  it  decomposed  spontaneously 
as  it  was  being  removed  from  the  desiccator. 

When  an  aqueous  solution  of  silver  nitrate  was  added  to  a  cold  aqueous  solution 
of  the  potassium  salt,  the  silver  nitrate  was  reduced  and  a  mirror  was  formed  upon  the 
walls  of  the  container.  This  reduction  was  caused  by  wobutyr-hydroxamic  acid  formed 
by  hydrolysis.  The  presence  of  the  hydroxamic  acid  was  verified  by  a  test  with  ferric 
chloride  and  by  the  formation  of  its  copper  salt. 

Summary. 

1.  The  preparation  and  properties  of  the  following  new  hydroxamic 
acids,  together  with  their  benzoyl  and  acetyl  esters,  are  described. — (1) 
cyclopropane-carboxyl-hydroxamic   acid;    (2)   wobutyr-hydroxamic   acid; 
(3)  dibenzylacet-hydroxamic  acid. 

The  sodium,  potassium  and  silver  salts  of  many  of  these  esters  were 
made,  and  the  conditions  under  which  these  salts  rearrange  were  determined 
and  compared. 

2.  The  conclusions  arrived  at  in  this  paper  are,  that  the  radicals  present 
in  the  acyl  groups  from  which  these  hydroxamic  acids  were  derived  in- 
fluence the  ease  with  which  their  derivatives  suffer  the  Beckmann  re- 
arrangement   in    the   following    order:    dibenzylmethyl    >    isopropyl    > 
benzylmethyl  >  cyclopropyl. 


423 

3.  During  the  investigation,  it  became  necessary  to  improve  the  methods 
employed  in  the  preparation  of  cyclopropane-monocarboxylic  acid  and  its 
ammonium  salt,  and  also,  to  synthesize  the  following  new  compounds: 
bi-dibenzylmethyl  urea  and  tribenzylmethyl  chloride.  The  failure  of 
tribenzylmethyl  chloride  to  react  with  magnesium  to  form  a  Grignard 
compound  is  discussed. 


Accepted  by  the  Department  of  Chemistry, 
October,  1921. 


53 


UNIVERSITY  OF  CALIFORNIA  UBRARY 


